Phase III, randomized, double-blind, placebo-controlled clinical study: a study on the safety and clinical efficacy of AZVUDINE in moderate COVID-19 patients
Sávio Bastos De Souza, Paula Gebe Abreu Cabral, Renato Martins Da Silva, Raul Ferraz Arruda, Sheila Passos De Figueiredo Cabral, Arícia Leone Evangelista Monteiro De Assis, Antônio Brazil Viana Junior, Wim Maurits Sylvain Degrave, Aline Dos Santos Moreira, Cléber Glória Silva, Junbiao Chang, Pingsheng Lei
Frontiers in Medicine, doi:10.3389/fmed.2023.1215916
Background: In 2019, a highly pathogenic coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) surfaced and resulted in the outbreak of coronavirus disease 2019 . With the aim of finding effective drugs to fight against the disease, several trials have been conducted since COVID-19 can only be considered a treatable disease, from a clinical point of view, after the availability of specific and effective antivirals. AZVUDINE (FNC), initially developed for treating HIV, is a potential treatment for COVID-19 as it has the capability to lower the patient's viral load and promote recovery. Methods: Volunteers infected with SARS-CoV-2 confirmed by reverse transcription polymerase chain reaction (RT-PCR), with good kidney and liver function, who were not using other antivirals or monoclonal antibodies were eligible. Samples from patients were assessed for viral load every 48 h during treatment using reverse transcription quantitative polymerase chain reaction (RT-qPCR) and droplet digital polymerase chain reaction (ddPCR). Results: The study's primary outcome measure was the percentage of participants showing an improvement in clinical scores, while the secondary outcome measure was the percentage of participants with a clinical outcome of cure. These measures were used to assess the safety and efficacy of FNC for treating COVID-19. In the analysis of sociodemographic variables, no significant differences were detected between patients in the FNC and the placebo group for race, age group, or sex. The results showed a potential benefit to participants who received FNC during the study, as observed in the shorter hospital stay, shorter negative conversion time of SARS-CoV-2, and a significant reduction in viral load. Furthermore, the reduction in fever and chills were significant at D1, D2, and D3.
Statistical analysis Initially, there were 342 participants in the study. However, due to the decrease in the number of COVID-19 cases in Brazil toward the end of 2021, the sample size was reevaluated and subsequently reduced to 180 participants. These participants were randomly assigned to two study groups, each consisting of 90 participants. All enrolled patients with moderate COVID-19 were hospitalized. The sample calculation was performed using the formula of "sample calculation for superiority studies using proportions, " described by World Health Organization (14) . To analyze demographic information and baseline eigenvalues, descriptive statistics such as mean, standard deviation, quartiles, and minimum and maximum values were calculated for numerical variables. Frequency and percentage were determined for categorical data. The appropriate statistical methods were employed to compare the two groups based on the type of indicator. The Mann-Whitney test was utilized to compare quantitative data, while Fisher's exact test was employed for categorical data. All statistical analyses were conducted using R-studio software.
Quantification of SARS-CoV-2 viral load by reverse transcription-polymerase chain reaction The MagMAXTM Viral/Pathogen Nucleic Acid Isolation kit (Applied Biosystems) was employed to extract total RNA from nasal and throat swabs obtained from the participants of the clinical study. The extraction process was carried out in accordance with the..
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